The blood coagulation mechanism takes the form of a cascade of enzymatic reactions at the end of which comes the formation of thrombin which finally converts fibrinogen into fibrin. Various procoagulant reactions such as, for example, the activation of prothrombin by factors Xa and Va are catalyzed by phospholipid surfaces to which the coagulation factors bind. Not every kind of phospholipid is capable of stimulating coagulation. The charging of the phospholipid surface appears to determine the extent of the effect. Negatively charged phospholipids such as phosphatidyl serine have a high procoagulatory effect.
Among the proteins which bind to phospholipids and interfere with processes dependent on phospholipid surfaces, there is a category which are dependent on Ca.sup.2+ in their binding to phospholipids. This category of proteins, which are also known as the annexines, includes not only lipocortin I, calpactin I, protein II, lipocortin III, p67-calelectrin but also the vascular anticoagulant protein (VAC) and IBC, PAP, PAPI, PP4, endonexin II and lipocortin V.
The structural features common to all the annexines are presumably the basis for their similar Ca.sup.2+ and phospholipid binding properties. Although this general property is true of all annexines, there is clear individuality in their affinity for Ca.sup.2+ and the various types of phospholipid.
The physiological functions of the annexines are concerned with membrane-associated processes. The fundamental mechanism of the coagulation-inhibiting effect of VAC was recognized as an inhibition of the catalytic capacity of phospholipids caused by the binding of VAC to their surfaces, thereby preventing the formation of the coagulation-promoting complex on the surface thereof.
Other annexines are also capable of inhibiting coagulation, but VAC appears to be the most effective inhibitor.
The aim of the present invention was to provide a VAC preparation which is more effective than pure VAC.